Mapping of cell-surface antigens is of great importance in medicine. Histocompatability antigen mapping reveals which donors of organs, or tissues such as blood, are most likely to be rejected or accepted by needful recipients of the same species. Tissue cells of donor and recipient must be well matched with respect to the different sets of cell surface antigens specific to the tissue to be transferred or transplanted. Matching helps to avoid foreign tissue rejection by the immune system, which functions to remove invasive cells i.e. those cells which do not originate from the selected recipient, and are often depicted as "non-self".
Such mapping is also of medical value in auto-immune disease, in which the organism rejects its own cells as if foreign, by immune reaction of auto antibodies against cells which are "self", i.e. they do originate from the selected recipient, but are not recognized as self. Rheumatic fever, Rheumatoid arthritis, Lupus Erythematosis are some examples of such disorders.
Mapping of cell antigens is useful in diagnosing and identifying normal differentiation antigens as well as antigens associated with various diseases.
The introduction by Kohler and Milstein in 1975 of a revolutionary new procedure for the routine production of monoclonal antibodies using hybridomas allows the production of almost unlimited quantities of antibodies of precise and reproducible specificity. While conventional antisera produced by immunizing animals with tumor cells or other antigens contain a myriad of antibodies differing in their specificity and properties, hybridomas produce a single antibody with uniform characteristics. The Kohler-Milstein procedure entails the fusion of spleen cells from an immunized animal with an immortal myeloma cell line. From the fused cells (hybridomas), clones are selected that produce antibody of the desired specificity (monoclonal antibody or mAb). As hybridoma cells can be cultured indefinitely (or stored frozen in liquid nitrogen), a constant supply of antibody is assured.
Antibodies are proteins that have the ability to combine with and recognize other molecules, known as antigens. Monoclonal antibodies are no different from other antibodies except that they are completely uniform in their properties and recognize only one antigen or a portion of an antigen known as a determinant.
In the case of cells, the determinant recognized is an antigen on or in the cell which reacts with the antibody. It is through these cell antigens that a particular antibody recognizes, i.e. reacts with, a particular kind of cell. Thus the cell antigens are markers by which the cell is identified.
These antigenic markers can be used to observe the normal process of cell differentiation and to locate abnormalities within a given cell system. The process of differentiation is accompanied by changes in the cell surface antigenic phenotype. Antigens that distinguish cells belonging to distinct differentiation lineages, or distinguish cells at different phases in the same differentiation lineage, can be observed if the correct antibody is available. Initial recognition of differentiation antigens came about through analysis of surface antigens of T-cell leukemias of the mouse and the description of the TL, Thy-1, and Lyt series of antigens. [Edward A. Boyse, Lloyd J. Old, Annual Review of Genetics 3,269-290, 1969]. The analysis of these T-cell differentiation antigens was greatly simplified by the availability of normal T cells and B cells of mouse and man and is relatively advanced, but less is known about differentiation antigens displayed on normal and neoplastic cells belonging to other lineages.
The hybridoma technology is exceptionally useful to determine cell surface composition i.e. cell surface phenotype. Preparation of a series of these hybridomas facilitates cell surface phenotype mapping since each hybridoma secrets its own monoclonal antibody specific for a tissue antigen. Groups of these can be prepared specific for any tissue or part thereof, by immunization with the cells or antigenic components of said tissue. A broad spectrum tissue antigen such as whole cells should produce an array of monoclonal antibodies. In the present work epidermal cell surface antigens are mapped. Identification of cell surface antigens and/or subclasses of cells such as keratinocytes is important for future diagnosis and treatment of diseases of epidermis.